Liver cancer, particularly hepatocellular carcinoma (HCC), remains a leading cause of cancer-related mortality worldwide. Chlorogenic acid (CGA), a dietary polyphenol abundant in coffee and plant-based foods, has emerged as a potential bioactive compound with anticancer and hepatoprotective properties. This systematic review aimed to evaluate the effects of CGA on liver cancer, focusing on its molecular mechanisms and potential synergistic or antagonistic interactions.

Records were screened using Rayyan, with duplicates removed and studies selected based on predefined inclusion and exclusion criteria. A total of 21 studies were included in the final analysis.

The included studies demonstrate that pure and CGA-containing extracts exert anticancer effects in preclinical liver cancer models. Mechanistically, CGA inhibits tumor cell proliferation, migration, and invasion, while inducing apoptosis and ferroptosis through key signaling pathways, including AMPK, ERK, and PTGS2/AKR1C3/GPX4. CGA also exhibits anti-inflammatory and antioxidant activities by regulating cytokine expression, NF-κB signaling, and cellular redox balance. In vivo studies support its hepatoprotective and tumor-suppressive effects, with dose-dependent responses observed. Additionally, CGA enhances the efficacy of certain chemotherapeutic agents, although antagonistic effects have been noted in radiotherapy contexts.

CGA demonstrates promising anticancer and hepatoprotective effects in liver cancer models through multi-target mechanisms. However, the current evidence is predominantly preclinical, and significant gaps remain regarding bioavailability, pharmacokinetics, and clinical efficacy.